The identification and functional analysis of lipid- or amino acid- responsive genes in pancreatic beta cells

利用小鼠胰腺β细胞系β HC9细胞，我们首次证实了脂肪酸转运蛋白（FATP）的主要异构体是FATP4，而ACBP（酰基辅酶a结合蛋白）没有发现新的异构体。然后，我们试图鉴定在1mM棕榈酸盐处理72小时后，其表达受到差异调节的基因，从而导致葡萄糖诱导的胰岛素分泌增强。我们采用了两种综合方法，即荧光差分显示（FDD； HIEROGLYPH， GENOMYX, Inc）和DNA微阵列（GeneChip system, Affymetrix, Inc）。虽然结果没有重叠，但我们总共获得了100多个脂质反应基因，包括新基因。我们还发现了一个日本病例高胰岛素血症与高氨血症（HI-HA综合征）由于激活突变在谷氨酸脱氢酶基因。由于氨基酸代谢与葡萄糖稳态的相互作用，病理生理学引起了人们的极大兴趣。

Using mouse pancreatic beta cell line, beta HC9 cells, we first demonstrated that major isoform of FATP (fatty acid transport protein) expressed was FATP4, and no novel isoform was found for ACBP (acyl-CoA binding protein). We then tried to identify genes whose expression was differentially regulated by 1mM palmitate treatment for 72 hours which resulted in the enhanced glucose-induced insulin secretion. We applied two comprehensive methods, namely, fluorescent differential display (FDD ; HIEROGLYPH, GENOMYX, Inc) and DNA microarray (GeneChip system, Affymetrix, Inc). Although the results did not have an overlap, altogether we obtained more than 100 lipid-responsive genes, including novel ones. We also identified a Japanese case of hyperinsulinism with hyperammonemia (HI-HA syndrome) due to an activating mutation in the glutamate dehydrogenase gene. The pathophysiology was of great interest as the interplay of amino acid metabolism and glucose homeostasis.